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2li8

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Revision as of 19:46, 1 August 2018

The solution structure of the Lin28-ZnF domains bound to AGGAGAU of pre-let-7 miRNA

Structural highlights

2li8 is a 2 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	2cqf
Gene:	CSDD1, Lin-28a, LIN28, LIN28A, ZCCHC1 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[LN28A_HUMAN] Acts as a 'translational enhancer', driving specific mRNAs to polysomes and thus increasing the efficiency of protein synthesis. Its association with the translational machinery and target mRNAs results in an increased number of initiation events per molecule of mRNA and, indirectly, in stabilizing the mRNAs. Binds IGF2 mRNA, MYOD1 mRNA, ARBP/36B4 ribosomal protein mRNA and its own mRNA. Essential for skeletal muscle differentiation program through the translational up-regulation of IGF2 expression (By similarity). Acts as a suppressor of microRNA (miRNA) biogenesis by specifically binding the precursor let-7 (pre-let-7), a miRNA precursor. Acts by binding pre-let-7 and recruiting ZCCHC11/TUT4 uridylyltransferase, leading to the terminal uridylation of pre-let-7. Uridylated pre-let-7 miRNAs fail to be processed by Dicer and undergo degradation. Degradation of pre-let-7 in embryonic stem (ES) cells contributes to the maintenance of ES cells. In contrast, LIN28A down-regulation in neural stem cells by miR-125, allows the processing of pre-let-7. Specifically recognizes the 5'-GGAG-3' motif in the terminal loop of pre-let-7. Also recognizes and binds non pre-let-7 pre-miRNAs that contain the 5'-GGAG-3' motif in the terminal loop, leading to their terminal uridylation and subsequent degradation.^[1] ^[2]

Publication Abstract from PubMed

Lin28 inhibits the biogenesis of let-7 miRNAs through a direct interaction with the terminal loop of pre-let-7. This interaction requires the zinc-knuckle domains of Lin28. We show that the zinc knuckle domains of Lin28 are sufficient to provide binding selectivity for pre-let-7 miRNAs and present the NMR structure of human Lin28 zinc knuckles bound to the short sequence 5'-AGGAGAU-3'. The structure reveals that each zinc knuckle recognizes an AG dinucleotide separated by a single nucleotide spacer. This defines a new 5'-NGNNG-3' consensus motif that explains how Lin28 selectively recognizes pre-let-7 family members. Binding assays in cell lysates and functional assays in cultured cells demonstrate that the interactions observed in the solution structure also occur between the full-length protein and members of the pre-let-7 family. The consensus sequence explains several seemingly disparate previously published observations on the binding properties of Lin28.

Structural basis of pre-let-7 miRNA recognition by the zinc knuckles of pluripotency factor Lin28.,Loughlin FE, Gebert LF, Towbin H, Brunschweiger A, Hall J, Allain FH Nat Struct Mol Biol. 2011 Dec 11;19(1):84-9. doi: 10.1038/nsmb.2202. PMID:22157959^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Heo I, Joo C, Cho J, Ha M, Han J, Kim VN. Lin28 mediates the terminal uridylation of let-7 precursor MicroRNA. Mol Cell. 2008 Oct 24;32(2):276-84. doi: 10.1016/j.molcel.2008.09.014. PMID:18951094 doi:http://dx.doi.org/10.1016/j.molcel.2008.09.014
↑ Heo I, Joo C, Kim YK, Ha M, Yoon MJ, Cho J, Yeom KH, Han J, Kim VN. TUT4 in concert with Lin28 suppresses microRNA biogenesis through pre-microRNA uridylation. Cell. 2009 Aug 21;138(4):696-708. doi: 10.1016/j.cell.2009.08.002. PMID:19703396 doi:http://dx.doi.org/10.1016/j.cell.2009.08.002
↑ Loughlin FE, Gebert LF, Towbin H, Brunschweiger A, Hall J, Allain FH. Structural basis of pre-let-7 miRNA recognition by the zinc knuckles of pluripotency factor Lin28. Nat Struct Mol Biol. 2011 Dec 11;19(1):84-9. doi: 10.1038/nsmb.2202. PMID:22157959 doi:10.1038/nsmb.2202

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2li8"

@@ Line 1: / Line 1: @@
 ==The solution structure of the Lin28-ZnF domains bound to AGGAGAU of pre-let-7 miRNA==
 <StructureSection load='2li8' size='340' side='right' caption='[[2li8]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2cqf|2cqf]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CSDD1, Lin-28a, LIN28, LIN28A, ZCCHC1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2li8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2li8 OCA], [http://pdbe.org/2li8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2li8 RCSB], [http://www.ebi.ac.uk/pdbsum/2li8 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2li8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2li8 OCA], [http://pdbe.org/2li8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2li8 RCSB], [http://www.ebi.ac.uk/pdbsum/2li8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2li8 ProSAT]</span></td></tr>
 </table>
 == Function ==

2li8

From Proteopedia

Revision as of 19:46, 1 August 2018

The solution structure of the Lin28-ZnF domains bound to AGGAGAU of pre-let-7 miRNA

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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